HSP90 inhibition induces cytotoxicity via down-regulation of Rad51 expression and DNA repair capacity in non-small cell lung cancer cells.
作者： Jen-Chung Ko , Huang-Jen Chen , Yu-Ching Huang , Sheng-Chieh Tseng , Shao-Hsing Weng
DOI: 10.1016/J.YRTPH.2012.10.003
关键词:
摘要: Abstract Heat shock protein 90 (HSP90) is an exciting new target in cancer therapy. Repair Rad51 involved protecting non-small cell lung (NSCLC) lines against chemotherapeutic agent-induced cytotoxicity. This study investigated the role of expression HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced cytotoxicity two NSCLC lines, A549 and H1975. The 17-AAG treatment decreased cellular mRNA levels phosphorylated MKK1/2-ERK1/2 levels, disrupted interaction. triggered degradation through 26S proteasome pathway. also cells’ DNA repair capacity, which was restored by forced Flag-Rad51 vector. Specific inhibition siRNA further enhanced 17-AAG-induced In contrast, ERK1/2 activation constitutively active MKK1/2 (MKK1/2-CA) vector significantly 17-AAG-reduced viability. Arachidin-1, antioxidant stilbenoid, augmented cytotoxic effect growth 17-AAG. arachidin-1-induced synergistic effects capacity were abrogated cells with MKK1/2-CA or transfection. conclusion, induces down-regulating cells.
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